CourseonStudyDesign.docVIP

 PAGE \* MERGEFORMAT 1 Course on Study Design Hands-On Session – Implementation of model based predictions using simulation/reestimation  PAGE \* MERGEFORMAT 5 Model-based design of dose finding studies Introduction: This exercise aims to illustrate simulation/reestimation-based evaluation of proposed designs. Based on models developed from data on a parallel group phase 2a (PoC) study (0, 5, 30 mg daily), different designs are evaluated with respect to their ability to precisely estimate parameters of a longitudinal model, as well as allow discrimination between model, both longitudinal and time-specific. The project team has planned to run a dose finding study with 5 doses (0, 5, 15, 30, 60 mg) and 60 subjects per arm using the same parallel group design as in phase 2a. Files provided: Data set: data1.csv data from the original POC trial (N=90, 30 per arm) data11.csv as data1.csv but with the proposed design (N=300, 60 per arm) data17.csv as data11.csv but N=3000 data19.csv 1 observation per subject (TIME=3) for 10 dose levels and N=10000 Model files: run10.mod = model implementing an Emax model run11.mod = as 10 but data set with proposed phase 2b design run12.mod = model with linear drug effect run13.mod = model without drug effect run14.mod = model for last time point only implementing an Emax model run15.mod = model for last time point only implementing a linear model run16.mod = model for last time point only without drug effect run19.mod = model for last time point change from baseline only Tasks: Explore an Emax model as an alternative to describe Phase 2a data In the original model development the final model was selected as a linear drug effect. This was (partially) based on parsimony. For the design of the dose finding study it is of interest to explore also other model structures and how informative designs are with respect to more complex models. Review run10.mod and then estimate and review output of the mode